Cortical Indices, DXA, and FRAX as Indicators of Bone Fragility: A Comparative Human Cadaveric Study

Abstract

Osteoporosis is a progressive skeletal disorder characterized by reduced bone mineral density (BMD) and increased risk of fragility fractures. Clinical assessment relies primarily on dual-energy X-ray absorptiometry (DXA) and the Fracture Risk Assessment Tool (FRAX), but limited access and low screening rates motivate investigation of complementary approaches. This human cadaveric study evaluated cortical indices of the second metacarpal, radius, and femur in relation to DXA-based osteoporosis status and biomechanically derived fracture susceptibility at the wrist and hip. Cortical measurements were obtained from 39 donor-matched forearms and femurs categorized as normal (n = 8), osteopenic (n = 11), and osteoporotic (n = 20) based on femoral neck DXA T-score. Simulated fall testing of the distal radius and proximal femur was performed to determine work to fracture, which was used to derive low and high biomechanical fracture susceptibility classifications. Among the cortical indices, metacarpal cortical index (MCI) demonstrated the strongest associations with DXA T-scores and biomechanical outcomes. MCI distinguished normal from osteoporotic classification at the femoral neck (area under the curve (AUC) = 0.938) and 1/3 radius (AUC = 0.986). For biomechanically derived fracture susceptibility, femoral neck T-score demonstrated strong discrimination at both the femur (AUC = 0.917) and wrist (AUC = 0.851), while MCI yielded AUCs of 0.847 and 0.855, respectively. FRAX hip fracture (HF) probability yielded AUCs of 0.911 at the femur and 0.830 at the wrist. These findings demonstrate associations between MCI, DXA-based osteoporosis status, and biomechanical fracture susceptibility in this cadaveric cohort. MCI may therefore warrant further investigation as a complementary screening approach, particularly where access to DXA is limited. Validation in larger clinical cohorts with prospective fracture outcomes is needed to determine its clinical utility.